Results of RELAX-AHF-2 to be revealed at Heart Failure 2017

28 Apr 2017

Prof. Marco Metra

Findings from the RELAX-AHF-2 trial, which assessed the efficacy, safety, and tolerability of serelaxin when added to standard care in patients with acute heart failure, will be announced and discussed during two presentations at Heart Failure 2017. A press release has already been issued.

Topic(s):

Heart Failure

RELAX-AHF-2 was an event-driven, multicentre, randomised, double-blind, placebo-controlled, phase III trial. It involved 6,600 patients hospitalised for acute heart failure and had two primary endpoints—reduction of cardiovascular death through day 180, and reduction of occurrence of worsening heart failure through day five.

Professor Marco Metra (University of Brescia, Brescia, Italy), who has co-chaired the trial with Professor John Teerlink (University of California San Francisco, San Francisco, USA) and who is giving one of the two presentations, outlined the rationale behind the trial: “The RELAX-AHF-2 trial is actually the third randomised placebo controlled trial with serelaxin versus placebo in acute heart failure. We conducted a phase IIB dose-finding study, which was called pre-RELAX, and was published in The Lancet in 2009. This established the dose of serelaxin that was then tested versus placebo in the RELAX-AHF-1 trial (published in The Lancet in 2013).”

Serelaxin, a relaxin receptor agonist, is a recombinant form of the naturally-occurring human relaxin-2 hormone. Human relaxin-2 is present in both men and women, and elevated levels in pregnant women are thought to help the body cope with the additional cardiovascular demands during pregnancy. In the phase IIB study, serelaxin was safe and well tolerated, with positive clinical outcome symptoms and signals in patients with acute heart failure. The RELAX-AHF-1 trial then tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo. It found that serelaxin was associated with dyspnoea relief, assessed by the Visual Analogue Scale but not by the Likert scale, but had no effect on readmission to hospital at 60 days. Notably, serelaxin treatment was well tolerated and was associated with a reduction in 180-day cardiovascular and all-cause mortality.

Prof. Metra commented: “The RELAX-AHF-1 trial of 1,161 patients with acute heart failure, randomised to serelaxin or placebo, failed on one of the two co-primary endpoints of dyspnoea relief and failed to show an improvement in the outcomes of 60-day mortality or hospitalisations. There was, however, an improvement in survival that was highly statistically significant.

“We know that once patients are hospitalised, or even undergo an emergency visit for a worsening of clinical symptoms of heart failure, their outcome is going to be much worse than that of someone who is an ambulatory outpatient. The subsequent increase in mortality can be up to 10-fold. Therefore, it makes sense to hypothesise that if we can interfere with some of the mechanisms causing the increase in subsequent mortality, we are able to improve the outcomes of the patient. This is why we performed the RELAX-AHF-2 trial.”

Acute heart failure is the most important cause of hospitalisation in patients over 65 years and the risk of mortality after hospitalisation is high, with approximately one in four to five patients not surviving a year afterwards. The results of RELAX-AHF-2 were widely anticipated because there has been no significant treatment breakthrough in improving mortality rates in acute heart failure for decades, despite major progress in treating other heart conditions, including chronic heart failure with reduced ejection fraction. The presentations will outline the key results of the study. Prof. John Teerlink will give the other of the two presentations.